In 2006, we created the University of Pittsburgh Clinical and Translational Science Institute (CTSI) as the academic home for clinical and translational science in western Pennsylvania. We revolutionized the practice of translational research at Pitt and at our partnering institution, the University of Pittsburgh Medical Center (UPMC), by training 850 translational scientists, incorporating team science in the promotions and tenure process, supporting 2225 investigators and 4049 research studies, and forging a collaborative research environment. We created and led the SPIRiT Consortium (6 CTSA hubs) and the NCATS Accrual to Clinical Trials network (21 CTSA hubs). Published manuscripts from a broad range of translational research studies that directly benefitted from CTSI support have been cited >81,000 times in the literature. Over the next 5 years, we will apply our infrastructure, training programs, best practices, and novel approaches to support translational science and scientists and to advance each of the national CTSA goals through our Overall Aims: 1) Workforce Development: Enhance and expand our diverse and team-oriented translational science workforce by providing them with the specialized skills, knowledge, and core competencies required to advance translation of their discoveries through innovative education methods, experiential training, and continuous learning opportunities; 2) Collaboration and Engagement: Engage an inclusive group of stakeholders as partners in the full translational research process and enable their contributions as members of teams conducting collaborative research; 3) Integration: Integrate into research programs those populations that have been traditionally excluded or studied in isolation and support and enhance studies that span the lifespan and translational research spectrum; 4) Methods/Processes: Promote innovation, quality, and efficiency across the translational research spectrum by developing and disseminating new research methodologies; adopting best practices from CTSA hubs, industry, and sectors outside of translational science; facilitating project management; and streamlining institutional research processes, with an emphasis on multi-center clinical trials; and 5) Informatics: Infuse informatics tools and methodologies across the research life cycle and translational research spectrum, efficiently integrate research and clinical data in a secure research data repository, and enable secure data sharing locally and nationally. In addition to the 7 required Components and our rigorous KL2 and TL1 training programs, we will expand our range and breadth of accomplishments through two Optional Components that leverage great strengths and opportunities in Innovation as a Discipline and Biomedical Modeling. Thus, the impact of CTSI, with its exceptional institutional support and committed and enthusiastic team, will continue to be significant, locally, regionally, and nationally.